SHBG levels correlate with insulin resistance in postmenopausal women

BackgroundOverweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated.Methods229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n = 125) and postmenopausal women (n = 104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured.ResultsNo significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p = 0.866).In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI.In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL.SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol.ConclusionsObesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women.These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.     

Women with normal glucose tolerance and a history of gestational diabetes show significant impairment of β-cell function at normal insulin sensitivity

ObjectiveAlthough the nature of gestational diabetes mellitus (GDM) remains unclear, the condition is thought to be related primarily to insulin resistance, overweight and obesity. Most studies include women with a history of GDM and later carbohydrate metabolism abnormalities, while reports of women with previous GDM and subsequent normoglycaemia are scarce. The aim of this study was to assess insulin resistance and β-cell function in normoglycaemic women with a history of GDM.Materials and methodsThe study group included 199 women, aged 38.4 ± 6.6 years, diagnosed with GDM within the last 5–12 years [GDM(+)] and a control group of 50 comparable women in whom GDM was excluded [GDM(−)], according to WHO criteria. Blood glucose and insulin levels were measured at the beginning (fasting) and at 60 and 120 min of oral glucose tolerance tests. Indices of insulin resistance (HOMA-IR), insulin sensitivity (HOMA-S%) and β-cell function (HOMA-B%) were calculated.ResultsNormoglycaemia was observed in 57% of GDM(+) and 88% of GDM(−) women (P = 0.0003). Diabetes was diagnosed in 13 (6.5%) GDM(+) women and in none of the GDM(−) women. Comparison of 113 normoglycaemic GDM(+) and 44 normoglycaemic GDM(−) women revealed significantly impaired β−cell function (HOMA-B%: 131.1 ± 51.1 vs 144.7 ± 47.1, respectively; P = 0.038) with similar normal body mass index (BMI) and no differences in HOMA-IR and HOMA-S%.ConclusionIn this study, more than half of the GDM(+) women were presented with normal glucose tolerance. However, despite normoglycaemia, women with a history of GDM were characterized by significantly impaired insulin secretion, but no signs of increased insulin resistance.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.     

Compare the effects of different visfatin concentration on cardiovascular risk factors,adiponectin and insulin resistance in patients with T2DM

AimThe discovery of new adipokine, visfatin can significantly enhance our knowledge of insulin resistance and diabetes mellitus. We explored the relation of visfatin concentrations to cardiovascular risk factors, adiponectin and insulin resistance criteria in patients with type 2 diabetes mellitus (T2DM).Materials and MethodsFifty-eight patients with T2DM were recruited from the out patients clinic of Shariati Hospital. Laboratory and anthropometric measurements include FBG, OGTT, HbA1c, fasting serum visfatin, insulin and adiponectin, HOMA-IR and hsCRP, weight, height, BMI and WHR were performed in all participants. All of the statistical data were analyzed using the SPSS15 software.ResultsThe log₁₀-transformed (log) plasma visfatin concentration was in significant positive correlation with age (r = 0.286, p = 0.033). Patients were divided in two groups by median log visfatin (0.85 ng/mL): group I had low values and group II had high values. In group I the log visfatin was in significant positive correlation with age (r = 0.436, p = 0.018) and in group II log visfatin was in significant negative correlation with FPG and HbA1c (r > 0.4, p < 0.05).ConclusionIn conclusion high circulating levels of visfatin could be in healthy relations with cardiovascular risk factors, insulin resistance status and adiponectin in diabetic patients.     

Relationship of raised serum total and protein bound sialic acid levels with hyperinsulinemia and indices of insulin sensitivity and insulin resistance in non-diabetic normotensive obese subjects

AimsObesity is known to be associated with cardiovascular disease and interaction between inflammation and insulin resistance is reported to enhance the cardiovascular risk in these subjects. The present study was designed to assess indices of insulin sensitivity, insulin resistance and sialic acid levels and their association in non-diabetic normotensives obese subjects.Materials and methodsThe present study was conducted in 30 obese male subjects and results were compared with 30 subjects with normal body weight. Insulin, total sialic acid and protein bound sialic acid were estimated in all the subjects. Insulin resistance was calculated by using Homeostatic Model Assessment-insulin resistance formula. Insulin sensitivity was assessed by quantitative insulin check index and insulin sensitivity index.ResultsInsulin resistance, serum total and protein bound sialic acid levels were significantly increased in obese cases as compared to non-obese controls. Total sialic acid showed significant positive correlation with HOMA-IR (p < 0.01), BMI (p < 0.01), waist and hip circumference (p < 0.01) and negative correlation with QUICKI (p < 0.01) and insulin sensitivity index (p = 0.018). There was no significant correlation between protein bound sialic acid and indices of insulin resistance and insulin sensitivity.ConclusionSialic acid levels are elevated in obese subjects and its association with insulin resistance and reduced insulin sensitivity may enhance the cardiovascular risk in these subjects.     

Impact of interleukin-1β antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: Results of secondary endpoints from a randomized,placebo-controlled trial

Aims/hypothesisThis study was conducted to determine the optimal monthly subcutaneous dose of canakinumab (a human monoclonal anti-human IL-1β antibody) needed to improve glucose control in metformin-treated patients with type 2 diabetes mellitus (T2DM).MethodsThis was a parallel-group, randomized, double-blind, multicentre, placebo-controlled study designed to assess the effect on HbA_1c and the safety/tolerability of four monthly doses of canakinumab (5, 15, 50, or 150 mg) as an add-on to metformin over 4 months.ResultsPatients (n = 551; mean age 54.1 years; mean baseline HbA_1c 7.4%) were randomized and treated in a double-blind fashion to canakinumab 5 mg (n = 93), 15 mg (n = 95), 50 mg (n = 92), 150 mg (n = 92) or placebo (n = 179) monthly. There was no dose response detected between active canakinumab doses, but all doses numerically lowered HbA_1c (primary endpoint) from baseline between 0.19% and 0.31% (placebo-unadjusted), with maximal effect noted in the 50 mg dose of canakinumab (−0.18% difference vs placebo; multiplicity-adjusted, P = 0.13902) as reported earlier (Ridker et al., 2012). No other glycaemic control parameters (FPG, fasting insulin, plasma glucose AUC_0–4h, 2-h PPG, peak glucose, C-peptide AUC_0–4h, peak C-peptide, insulin AUC_0–4h, peak insulin, ISR_0–2h, HOMA-β and HOMA-IR) showed any meaningful changes by canakinumab therapy. Canakinumab treatment was safe and well tolerated. There were no relevant differences in adverse events between the canakinumab and placebo groups.Conclusions/interpretationA 4-month course of monthly canakinumab (50 mg) produced a numerical reduction of HbA_1c in T2DM patients on metformin, potentially by improving beta-cell function. The safety and tolerability profile of canakinumab was consistent with prior trials.Trial registrationRegistry: http://www.ClinicalTrials.gov, Registration No.: NCT00900146     

Insulin resistance is associated with Fibroblast Growth Factor-23 in stage 3–5 chronic kidney disease patients

AimTo determine the associations between insulin resistance, fibroblast growth factor 23 (FGF-23), and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients.IntroductionFGF-23 is associated with atherosclerosis and cardiovascular disease, but its association with insulin resistance in CKD has not been explored.SubjectsCross sectional study of 72 stage 3–5 CKD patients receiving care in Ontario, Canada.Materials and MethodsInsulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR), FGF-23 was measured by carboxyl terminal enzyme linked immunoassay (ctFGF-23) and CAC was measured by multi-slice computed tomography.ResultsMedian HOMA-IR was 2.19 μU/ml (interquartile range 1.19 to 3.94). Patients with HOMA-IR > 2.2 had greater ctFGF-23 (179.7 vs 109.6; P = 0.03), and 40% higher log CAC scores (2.09 ± 0.87 vs 1.58 ± 1.26; P = 0.049). Multivariable linear regression adjusted for 1,25 dihydroxyvitamin D, kidney function, and parathyroid hormone revealed insulin resistance was a risk factor for greater log ctFGF-23 levels (log HOMA IR β = 0.37; 95% confidence interval 0.14 to 0.59; P = 0.002).ConclusionsInsulin resistant CKD patients demonstrated higher FGF-23 levels, and increased CAC, while PO₄ levels remained normal, suggesting a potential link between insulin resistance and PO₄ homeostasis in CKD.     

Association of vitamin D deficiency and insulin resistance with breast cancer in premenopausal Algerian women: A cross-sectional study

BackgroundLow 25(OH)D levels are mainly related to breast cancer (BC) risk in postmenopausal women, while the impact of insulin resistance (IR) on BC prognosis is controversial.ObjectiveConsidering the high prevalence of BC in younger Algerian women, this cross-sectional study analyzed whether vitamin D status and IR are biomarkers for breast tumor status in premenopausal women.MethodsIn 96 women (mean age, 40.96 ± 0.65years) newly diagnosed with BC, tumor status was determined immunohistochemically, classified by molecular subtype, then correlated with body-mass index, total plasma 25(OH)D, insulin and glucose levels and HOMA-IR, using Chi², Student t, Spearman and ANOVA tests and multivariate logistic regression.ResultsA total of 66 of the 96 patients (68.75%) showed vitamin D deficiency (9.74 ng/mL). Overweight and obese patients with HOMA-IR > 2.5, positive for HER2 and with high Ki-67 index had the most severe vitamin D deficiency. There was a significant association between vitamin D deficiency, high Ki-67 index (OR, 14.55; 95% CI: 3.43–82.59; P = 0.00078) and IR (OR, 4.99; 95% CI: 1.27–24.47; P = 0.03), and between IR and HER2-positivity (OR, 3.23; 95% CI: 1.05–10.56; P = 0.04).ConclusionsVitamin D deficiency and IR are potential biomarkers for poorer prognosis in BC patients, independently of and/or synergically with high Ki-67 index and HER2-positivity in premenopausal overweight or obese women. The potential relationship of vitamin D receptor gene expression with breast cancer survival in Algerian patients will be investigated in a large cohort.     

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes

AimsShort-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes.MethodsIn this study, 63 patients (age 59 ± 8.3 years, baseline A1c 6.8 ± 0.7%, diabetes duration 3.0 ± 2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR).ResultsAs expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P = 0.02), decreased HOMA-IR (P < 0.001), and reduced AUC_glucagon (P < 0.001). Of note, however, IIT had no significant impact on AUC_GLP-1 (P = 0.24) and reduced AUC_GIP (P = 0.02).ConclusionDespite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.     

Association of insulin resistance,insulin and leptin levels with coronary in-stent restenosis

BackgroundIn-stent restenosis remains the major limitation of coronary stent implantation. Leptin is a hormone strongly related to insulin resistance (IR). Moreover, insulin resistance and hyperinsulinemia are common in patients with coronary heart disease (CHD), each of the previous metabolic and hormonal factors might be involved in restenosis after stent implantation.ObjectiveThis study was planned to evaluate the relationship between insulin resistance, insulin, leptin levels and coronary in-stent restenosis after coronary stent implantation in non-diabetic patients with CHD and to determine their value in prediction of restenosis.Patients and methodsThe study included 48 non-diabetic CHD patients with previous successful coronary stent implantation. They were divided into two groups according to the presence of in-stent restenosis on follow-up coronary angiography (6–9 months after stent implantation). The first group was CHD patients with in-stent restenosis which included 20 patients, the second group was CHD patients without restenosis which included 28 patients. All patients were subjected to complete clinical examination including determination of body mass index (BMI), waist to hip ratio (WHR) and laboratory investigations including fasting plasma glucose (FPG), fasting plasma insulin (FP insulin), lipid profile (total cholesterol, HDL-C, LDL-C, TG), glycoselated hemoglobin (HbA1c), plasma leptin, estimation of homeostasis model assessment of IR (HOMA-IR). All subjects were submitted to OGTT with estimation of 2-h post-prandial glucose (2-hPP glucose) and sum post-prandial insulin levels (sum PP insulin). Follow-up coronary angiography was done for all patients with the estimation of minimal luminal diameter (MLD), diameter stenosis % and late lumen loss.ResultsThere was highly significant increase in each of FP insulin, sum PP insulin, HOMA-IR, leptin, diameter stenosis % and late lumen loss (P < 0.001) and a highly significant decrease of MLD (P < 0.001) in CHD patients with in-stent restenosis when compared to CHD patients without in-stent restenosis. MLD is negatively correlated to each of FP insulin (r = −0.49, P < 0.001), sum PP insulin (r = −0.60, P < 0.001) HOMA-IR (r = −0.63, P < 0.001) and leptin (r = −0.55, P < 0.001) while late lumen loss was positively correlated to each of FP insulin (r = 0.98, P < 0.001), sum PP insulin (r = 0.70, P < 0.001), HOMA-IR (r = 0.67, P < 0.001) and leptin (r = 0.72, P < 0.001). Multiple regression analysis revealed that each of FP insulin, sum PP insulin, HOMA-IR and leptin can be considered an independent predictor of in-stent restenosis (P < 0.001).ConclusionOur study revealed that insulin resistance, fasting and post-prandial hyperinsulinemia and hyperliptinemia are considered predictors of coronary in-stent restenosis. Evaluation of HOMA-IR, insulin levels after standard OGTT and leptin levels are important tools in an attempt to recognize subjects at risk of early restenosis among non-diabetic, CHD patients undergoing percutaneous coronary revascularization and stent implantation.     

Effect of cigarette smoking on insulin resistance risk

ObjectivesSmoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics.Study designThis study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6 ± 16.0 and 38.5 ± 21.9 years. All subjects are not diabetic.MethodsFasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR = [fasting insulin (mU/L) × fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance.ResultsCompared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine.ConclusionOur results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers.     

Effects of acute hyperinsulinaemia on total and high-molecular-weight adiponectin concentration in metabolically healthy but obese postmenopausal women: A Montreal–Ottawa New Emerging Team (MONET) study

AimThe aim of this study was to determine the differences and changes in total and high-molecular-weight (HMW) adiponectin levels among metabolically healthy but obese (MHO) postmenopausal women in response to acute hyperinsulinaemia.MethodIn this cross-sectional study, 55 non-diabetic overweight and obese postmenopausal women underwent a hyperinsulinaemic–euglycaemic clamp test to evaluate insulin sensitivity. Subjects within the upper tertile of insulin sensitivity were described as ‘MHO’ (n = 18), whereas those within the lowest tertile were considered ‘at risk’ (n = 18). Plasma total and HMW adiponectin levels were measured by ELISA at 0 (baseline), 90, 160 and 180 min during the clamp.ResultsAt baseline and at all time points during the clamp, MHO individuals had significantly higher total and HMW adiponectin levels than at-risk subjects (AUC: total adiponectin = 2506 ± 1010 vs 1616 ± 830; HMW adiponectin = 909 ± 307 vs 604 ± 349; P < 0.05). In addition, a significant reduction in total adiponectin was observed at 160 min and 180 min in at-risk and MHO subjects, respectively, while HMW adiponectin significantly decreased at 160 min in at-risk subjects, and at 90 min as well as 160 min in MHO women.ConclusionMHO postmenopausal women had higher levels of plasma total and HMW adiponectin than at-risk subjects at baseline and during the clamp. Furthermore, significant decreases in total and HMW adiponectin were observed at certain time points in both the MHO and at-risk subjects.     

Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery

AimObesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery.MethodsThirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n = 11) or insulin-resistant (n = 12), based on the Matsuda insulin sensitivity index (ISI_Matsuda). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only).ResultsDespite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (P < 0.05), and associated with IR as assessed by both ISI_Matsuda (r = −0.417, P = 0.038) and HOMA-IR (r = 0.464, P = 0.007) at baseline, whereas VAT fibrosis was not. Six months after surgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (P < 0.0001). No correlation was found between SAT fibrosis and IR after surgery.ConclusionOverall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans.     

Metabolic disturbances after acute vascular events: A comparative study of acute coronary syndrome and ischaemic atherothrombotic stroke

ObjectiveThis pilot study aimed to compare metabolic disturbances, particularly insulin resistance (IR) and cardiovascular risk factors (CRFs), following two types of acute vascular atherothrombotic disease events: ischaemic atherothrombotic stroke (AS); and acute coronary syndrome (ACS).Design and methodsA total of 110 non-diabetic patients presenting with either AS (n = 55) or ACS (n = 55) were included in our prospective comparative study, and matched for age and gender. IR was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR) method, and each patient's personal and family history were also recorded.ResultsIR was significantly higher in the ACS vs AS group (HOMA-IR index 2.17 ± 1.90 vs 1.50 ± 0.81, respectively; P = 0.03). The AS group had a significantly higher prevalence of personal history of hypertension (51% vs 31%; P = 0.03), while current smoking was more prevalent in the ACS group (30% vs 18%; P = 0.04). There were no significant differences between the two groups as regards any other CRFs.ConclusionThe distribution of CRFs varied depending on the vascular event, and metabolic disturbances differed according to the atherothrombotic disease. IR was greater after ACS than AS.     

Impact of objectively measured sedentary behaviour on changes in insulin resistance and secretion over 3 years in the RISC study: Interaction with weight gain

AimsThe importance of reducing sedentary time is increasingly being recognized in the prevention of diabetes and cardiovascular disease. Despite this, the prospective association between sedentary time and physical activity with insulin sensitivity and cardiometabolic risk factors has been little studied.MethodsIn an analysis of data from the European RISC study, sedentary time and time spent in activity of moderate or vigorous intensity were assessed by accelerometry at baseline in 313 men and 414 women, aged 30–60 years, with insulin sensitivity as measured by euglycaemic–hyperinsulinaemic clamp. Three years later, cardiometabolic risk factors (anthropometry, glucose, insulin, lipids) were available for 549 participants.ResultsIn cross-sectional analyses using baseline data, after adjusting for age, gender, recruitment centre and time spent in activity of moderate or vigorous intensity, significant unfavourable associations were observed between higher sedentary time with body weight, HDL cholesterol, triglycerides, clamp-measured insulin sensitivity and insulin secretion (all P_trend < 0.002). Sedentary time remained significantly associated with insulin secretion after adjusting for insulin sensitivity (P_trend = 0.02). In longitudinal analyses, higher baseline sedentary time was associated with 3-year increases in fasting glucose, fasting insulin and the HOMA insulin-resistance index score for the 50% of the study population who increased their BMI by at least 0.3 kg/m² (all P_trend < 0.01); these relationships remained significant after adjusting for time spent in activity of moderate or vigorous intensity. The 3-year increase in insulin secretion was lower in those spending more time doing activity of moderate or vigorous intensity (P_trend = 0.03).ConclusionThese prospective data suggest that less sedentary behaviour may partly counteract some of the negative effects of increasing body weight on glucose–insulin homoeostasis.     

Assessment of insulin resistance using surrogate markers in patients of metabolic syndrome

BackgroundInsulin resistance is defined as situation where there is insufficient biological or metabolic response to normal plasma levels of insulin. For precise quantification of insulin sensitivity, the euglycemic hyperinsulinemic clamp may be used, but it is expensive, invasive and used mainly in research settings. HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) and ISI 0,120 (Insulin Sensitivity Index) are indirect markers of insulin resistance. The present study evaluated the usefulness of the surrogate markers for evaluation of Insulin resistance in clinical settings.MethodThis study was carried out on 120 subjects. Of these, 60 subjects presenting with two or more features of metabolic syndrome (Hypertension, Obesity, Dyslipidemia, altered glucose tolerance) were included in the study group. Sixty age and sex matched healthy controls were selected with normal Body mass index. All the subjects underwent a standard Oral Glucose Tolerance Test. Plasma glucose and serum insulin were estimated using Glucose oxidase and ELISA principle respectively. HOMA-IR and ISI 0,120 were calculated using relevant formulae.ResultThe HOMA-IR values were significantly raised in suspected Insulin resistant subjects (6.74 ± 1.24) as compared to healthy controls (0.82 ± 0.017) (p = 0.001). ISI 01,20 was significantly low in insulin resistant subjects (3.13 ± 0.17) as compared to controls (20.60 ± 0.37) (p < 0.001). Insulin sensitivity index showed a significant negative correlation with HOMA-IR. A significant negative correlation was observed between serum cholesterol, serum LDL-cholesterol and ISI 0,120 indicating that dyslipidemia in metabolic syndrome may result from a decrease in Insulin sensitivity.ConclusionHOMA-IR and ISI 0,120 are simple, convenient and sensitive estimates of insulin resistance adaptable for use in clinical practice as well as large-scale epidemiological studies.     

Validation of a simple index (SIisOGTT) of insulin sensitivity in a population of sedentary men

AimThe ongoing obesity epidemic is associated with numerous health problems related to altered metabolic function. Among these is type 2 diabetes, characterized by lowered insulin sensitivity (IS). Consequently, the development of simple indices to assess IS has research and clinical importance. The SI_isOGTT, a new index of IS, was recently described by Bastard et al. (Diabetes & Metabolism 2007;33:261–8), and validated in sedentary, non-diabetic, overweight and obese postmenopausal women. The aim of the present study was to validate the index in men.MethodsThe data used in this project came from sedentary men (n = 36), aged 34–53 years, all of whom underwent a hyperinsulinaemic–euglycaemic clamp and 2-hour oral glucose tolerance test (OGTT). Correlations with M/I (glucose infusion rate [GIR] divided by insulin concentration), GIR and GIR divided by fat-free mass (FFM) were obtained by four well-known indices (HOMA, QUICKI, Cederholm and Matsuda) as well as with the new SI_isOGTT index. Pearson correlations and Bland–Altman analyses were obtained for every index versus clamp value.ResultsThe best correlate of IS in the present study was the SI_isOGTT (r = 0.84, P < 0.0001). The agreement of this method with the hyperinsulinaemic–euglycaemic clamp, as assessed by Bland–Altman plots, was similar to those of the other indices and to those previously described in postmenopausal women.ConclusionThe new index proposed by Bastard et al. is as good a predictor of IS in sedentary men as the other commonly used indices, and appears to be as reliable in this population as it was in the original study of postmenopausal women.     

Effect of Exercise Therapy on Monocyte and Neutrophil Counts in Overweight Women

IntroductionIt has been well known that physical inactivity is associated with a significantly higher incidence of coronary artery disease. This study aimed to test our hypothesis that endurance aerobic exercise training has cardiovascular protective effects as a result of inhibiting inflammatory processes.MethodsForty-two overweight women [age, 53.4 ± 9.8 years; body mass index (BMI), 28.0 ± 2.8] received electric bicycle ergometer exercise therapy at the lactate threshold intensity for 30 to 60 minutes per day, 1 to 6 times per week for 6 weeks. The exercise training was performed within the possible load (exercise duration and frequency) for each subject.ResultsLeukocyte, monocyte, and neutrophil counts significantly decreased after the exercise therapy (P < 0.05). In simple regression analysis, percent changes in monocyte and neutrophil counts were correlated with percent changes in fasting triglyceride levels, insulin sensitivity index, BMI, and maximal oxygen uptake (VO₂max). In stepwise multiple regression analysis, the percent change in monocyte counts was associated with percent changes in fasting triglyceride and VO₂max (r² = 0.368, P < 0.001), and the percent change in neutrophil counts was associated with percent changes in insulin sensitivity index and BMI (r² = 0.292, P < 0.001).ConclusionsEndurance aerobic exercise training can influence some inflammatory processes. Furthermore, increased aerobic capacity may be antiinflammatory and have cardiovascular protective effects in overweight women.     

Common single nucleotide polymorphisms in the FNDC5 gene are associated with glucose metabolism but do not affect serum irisin levels in Japanese men with low fitness levels

ObjectiveThis cross-sectional study analyzed the association of serum irisin concentrations with cardiorespiratory fitness levels and common single nucleotide polymorphisms (SNPs) in the FNDC5 gene and examined the relationships between cardiorespiratory fitness levels, common SNPs in FNDC5, and glucose metabolism.Materials/MethodsCardiorespiratory fitness was assessed by measuring peak oxygen uptake (VO₂peak) and serum irisin levels by ELISA in 163 Japanese men (age, 21–79 years). Subjects were divided into low- and high-fitness groups within each age group according to the median VO₂peak value. Common SNPs (rs3480 and rs16835198) of the FNDC5 gene were genotyped with the TaqMan assay. Glucose metabolism was evaluated by measuring HbA1c, fasting plasma glucose (FPG), insulin levels, and HOMA-IR.ResultsSerum irisin levels were negatively correlated with age (p < 0.001) and not associated with the VO₂peak or HOMA-IR. In the low-fitness group, SNP analysis revealed that subjects with the rs3480 AG and GG genotypes had higher levels of insulin and HOMA-IR than those with the AA genotype (p < 0.01; no significant difference was observed in the high-fitness group). The GG genotypes of rs16835198 were associated with increased HbA1c and FPG in the low-fitness group only (p < 0.05). SNPs and both fitness groups were not associated with serum irisin levels.ConclusionsIn Japanese men, cardiorespiratory fitness levels and common SNPs in FNDC5 are not associated with circulating irisin levels, whereas high cardiorespiratory fitness abolishes the association between the rs3480 and rs16835198 SNPs and glucose metabolism independent of serum irisin levels.     

C-reactive protein levels are inversely correlated with the apolipoprotein B-48-containing triglyceride-rich lipoprotein production rate in insulin resistant men

The pro-inflammatory state and elevated plasma levels of post-prandial triglycerides (TG) are associated with increased cardiovascular disease risk. Recent studies suggested that the increase in the production rate of post-prandial lipoproteins observed in patients with insulin resistance (IR) may be caused, at least in part, by the dysregulation of intestinal insulin sensitivity triggered by inflammation.ObjectiveThe objective of the present study was to evaluate the association between IR, plasma C-reactive protein (CRP) levels and the kinetics of TG-rich lipoprotein (TRL) containing apolipoprotein (apo) B-48 in a large sample of insulin sensitive (IS) and IR men.MethodsThe in vivo kinetics of TRL apoB-48 were measured in 151 men following a primed-constant infusion of l-[5,5,5-D₃]leucine. IR subjects (n = 91) were characterized by fasting TG levels ≥ 1.5 mmol/L and an index of homeostasis model assessment of IR (HOMA-IR) ≥ 2.5 or type 2 diabetes, while IS subjects (n = 24) were characterized by an HOMA-IR index < 2.5 and TG levels < 1.5 mmol/L.ResultsIR subjects had higher TRL apoB-48 production rate (+ 202%; P < 0.0001) and CRP levels (+ 51%; P = 0.01) than IS subjects. TRL apoB-48 production rate and CRP levels were inversely correlated in IR subjects (r = − 0.32; P = 0.002). IR subjects with CRP levels above the median (2.20 mg/L) had lower TRL apoB-48 production rate than IR subjects with CRP levels below the median (Δ = − 24%; P < 0.05).ConclusionOur results confirm that IR is associated with increased TRL apoB-48 secretion and suggest that a higher inflammatory status is associated with decreased TRL apoB-48 secretion among IR subjects.